This target trial emulation study showed no statistically significant difference in survival or favorable neurologic outcome between lidocaine and amiodarone in refractory, shockable, out-of-hospital cardiac arrest.
Both amiodarone and lidocaine are guideline-supported therapies for refractory shockable OHCA, but the optimal first-line agent is unclear. Although early trials favored amiodarone, the ROC-ALPS trial found no survival or neurologic benefit for either drug, and more recent observational studies have suggested a possible advantage for lidocaine.
This target trial emulation utilized the Resuscitation Outcomes Consortium Cardiac Epistry to compare lidocaine (n=987) with amiodarone (n=1464) in adults with atraumatic, shockable OHCA refractory to at least three defibrillation attempts. Because the study used cases from 2011–2015, when ACLS guidelines recommended amiodarone as first-line, investigators used inverse probability weighting and doubly robust regression to reduce treatment-selection bias. Lidocaine was associated with higher rates of ROSC at ED arrival (41.0% vs. 34.6%; absolute difference 6.43%; 95%CI 2.6–10.3%) but not with significantly improved survival to hospital discharge (26.2% vs. 23.5%; absolute difference 2.78%; 95%CI–0.6 to 6.2%) or favorable neurologic outcome (17.7% vs. 16.2%; absolute difference 1.5%; 95%CI–1.5 to 4.5%). Although appropriately cautious in their interpretation, the authors suggest the upper bounds of the confidence intervals leave open the possibility for clinically meaningful benefit of lidocaine. While the target trial emulation strengthens causal inference compared to traditional observational analyses, the study still has severe limitations when it comes to drawing any conclusions of superiority, including the older registry data with potentially outdated practices, the inability to assess timing of antiarrhythmic administration, and the potential for residual confounding.
How does this change my practice?
I lean toward amiodarone, partially because that’s what I was trained to use and what the nurses at my institution are most comfortable giving. My practice is to administer an antiarrhythmic early in VF/pVT, probably earlier than many clinicians and certainly earlier than ACLS introduces it. I’m also willing to switch agents later in the resuscitation if still refractory. If a resident wants to
start with lidocaine, that is also a reasonable and evidence-based approach, although I will continue reaching for amiodarone first until more definitive evidence emerges. Timing may matter more than which drug is selected, a question this target trial emulation was not designed to address.
Lidocaine versus amiodarone in patients with shockable out-of-hospital cardiac arrest: a target trial emulation. Crit Care Med. 2026 Jul 15. doi: 10.1097/CCM.0000000000007265. Online ahead of print. PMID: 42456091.
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